A covalent adduct of MbtN, an acyl-ACP dehydrogenase from Mycobacterium tuberculosis, reveals an unusual acyl-binding pocket.

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis. Access to iron in host macrophages depends on iron-chelating siderophores called mycobactins and is strongly correlated with Mtb virulence. Here, the crystal structure of an Mtb enzyme involved in mycobactin biosynthesis, MbtN, in complex with its FAD cofactor is presented at 2.

Purification, crystallization and preliminary X-ray studies of MbtN (Rv1346) from Mycobacterium tuberculosis.

In Mycobacterium tuberculosis, the protein MbtN (Rv1346) catalyzes the formation of a double bond in the fatty-acyl moiety of the siderophore mycobactin, which is used by this organism to acquire essential iron. MbtN is homologous to acyl-CoA dehydrogenases, whose general role is to catalyze the α,β-dehydrogenation of fatty-acyl-CoA conjugates. Mycobactins, however, contain a long unsaturated fatty-acid chain with an unusual cis double bond conjugated to the carbonyl group of the mycobactin core.